Broccoli Consumption Alters Microbial Diversity, Metatranscriptome, and Host Transcriptome in Mice Fed a Total Western Diet.

Background: Cruciferous vegetables (CVs) are a source of dietary fiber and phytochemicals that alter the microbiome in animals and humans. Constituent cruciferous vegetable compounds, such as glucosinolates, have demonstrated anti-inflammatory properties in animal models, though often using doses and basal diets that are not relevant to humans. The mechanism(s) is unclear, but the gut microbiota may metabolize these compounds into bioactive molecules that influence immune pathways.

Sequential transcriptional gates in the thalamo-cortical circuit coordinate memory stabilization.

The molecular mechanisms that enable memories to persist over long time-scales from days to weeks and months are still poorly understood. To develop insights we created a behavioral task where, by varying the frequency of learned associations, mice formed multiple memories but only consolidated some, while forgetting others, over the span of weeks. We then monitored circuit-specific molecular programs that diverge between consolidated and forgotten memories.

Protocol for the development of a core outcome set for type 1 diabetes risk screening.

Introduction: Type 1 diabetes is a chronic autoimmune disease that often presents with diabetic ketoacidosis at diagnosis. Since detection of type 1 diabetes risk is possible using genetic risk scores and autoantibody assays, prevention of diabetic ketoacidosis or delayed onset of type 1 diabetes may be possible and may improve outcomes. Several pilot screening programmes for type 1 diabetes risk have emerged worldwide but outcomes measured in these screening programmes are heterogeneous, making it difficult to compare and synthesise findings across studies.

A type 4 resistant potato starch alters the cecal microbiome, gene expression and resistance to colitis in mice fed a Western diet based on NHANES data.

Four major types of resistant starch (RS1-4) are present in foods and can be fermented to produce short-chain fatty acids (SCFAs), alter the microbiome and modulate post-prandial glucose metabolism. While studies in rodents have examined the effects of RS4 consumption on the microbiome, fewer have examined its effect on gene expression in the cecum or colon or resistance to bacterial-induced colitis, and those that have, use diets that do not reflect what is typically consumed by humans. Here we fed mice a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data for 6-7 weeks and then supplemented their diet with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch.

Hospitalised older adults with community-acquired pneumonia and sepsis have dysregulated neutrophil function but preserved glycolysis.

Objective: Community-acquired pneumonia (CAP) is a leading cause of hospitalisation in older adults and is associated with a high likelihood of adverse outcomes. Given the ageing population and lack of therapeutic advances in CAP, new strategies to manage the burden of this disease are needed. Neutrophil dysfunction has been widely demonstrated in CAP and is associated with poor outcomes.

A novel cell model of the proteinase/antiproteinase balance observed in alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging.

A type 4 resistant potato starch alters the cecal microbiome and gene expression in mice fed a western diet based on NHANES data.

Four major types of resistant starch (RS1-4) are present in foods, all of which can alter the microbiome and are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs). Type 4 RSs are chemically modified starches, not normally found in foods, but have become a popular food additive as their addition increases fiber content. Multiple studies, in humans and rodents, have explored how different RS4 affect post-prandial glucose metabolism, but fewer studies have examined the effects of RS4 consumption on the microbiome.

Efficient adsorption and photocatalytic degradation of water emerging contaminants through nanoarchitectonics of pore sizes and optical properties of zirconium-based MOFs.

Over the past decades, the presence of pharmaceutical emerging contaminants in water bodies is receiving increasing attention due to the high concentration detected from wastewater effluent. Water systems contain a wide range of components coexisting together, which increases the difficulty of removing pollutants from the water. In order to achieve selective photodegradation and to enhance the photocatalytic activity of the photocatalyst on emerging contaminants, a Zr-based metal-organic framework (MOF), termed VNU-1 (VNU represents Vietnam National University) constructed with ditopic linker 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene (HCPEB), with enlarged pore size and ameliorated optical properties, was synthesized and applied in this study.

Raw potato starch alters the microbiome, colon and cecal gene expression, and resistance to infection in mice fed a Western diet.

Resistant starches (RS) are fermented in the cecum and colon to produce short-chain fatty acids and other microbial metabolites that can alter host physiology and the composition of the microbiome. We previously showed that mice fed a Total Western Diet (TWD) based on NHANES data that mimics the composition of a typical American diet, containing resistant potato starch (RPS), produced concentration dependent changes to the cecal short-chain fatty acids, the microbiome composition as well as gene expression changes in the cecum and colon that were most prevalent in mice fed the 10% RPS diet. We were then interested in whether feeding TWD/RPS would alter the resistance to bacterial-induced colitis caused by (), a mouse pathogen that shares 66.

Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics.

Correction: Solano-Aguilar et al. Fruit and Vegetable Supplemented Diet Modulates the Pig Transcriptome and Microbiome after a Two-Week Feeding Intervention. 2021, , 4350.

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The evolutionary dynamics of extrachromosomal DNA in human cancers.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection.

Therapeutic targeting of ATR in alveolar rhabdomyosarcoma.

Despite advances in multi-modal treatment approaches, clinical outcomes of patients suffering from PAX3-FOXO1 fusion oncogene-expressing alveolar rhabdomyosarcoma (ARMS) remain dismal. Here we show that PAX3-FOXO1-expressing ARMS cells are sensitive to pharmacological ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Expression of PAX3-FOXO1 in muscle progenitor cells is not only sufficient to increase sensitivity to ATR inhibition, but PAX3-FOXO1-expressing rhabdomyosarcoma cells also exhibit increased sensitivity to structurally diverse inhibitors of ATR.

Target actionability review to evaluate CDK4/6 as a therapeutic target in paediatric solid and brain tumours.

Background: Childhood cancer is still a leading cause of death around the world. To improve outcomes, there is an urgent need for tailored treatment. The systematic evaluation of existing preclinical data can provide an overview of what is known and identify gaps in the current knowledge.

Resistant Potato Starch Alters the Cecal Microbiome and Gene Expression in Mice Fed a Western Diet Based on NHANES Data.

Several studies indicate that the four major types of resistant starch (RS1-4) are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs) and can alter the microbiome and host physiology. However, nearly all these studies were conducted in rodents fed with a diet that does not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD) based on National Health and Nutrition Examination Survey (NHANES) data that mimics the macro and micronutrient composition of a typical American diet for 6 weeks and then supplemented with 0, 2, 5, or 10% of the RS2, resistant potato starch (RPS), for an additional 3 weeks.

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21.

Fruit and Vegetable Supplemented Diet Modulates the Pig Transcriptome and Microbiome after a Two-Week Feeding Intervention.

A study was conducted to determine the effects of a diet supplemented with fruits and vegetables (FV) on the host whole blood cell (WBC) transcriptome and the composition and function of the intestinal microbiome. Nine six-week-old pigs were fed a pig grower diet alone or supplemented with lyophilized FV equivalent to half the daily recommended amount prescribed for humans by the Dietary Guideline for Americans (DGA) for two weeks. Host transcriptome changes in the WBC were evaluated by RNA sequencing.

ecDNA hubs drive cooperative intermolecular oncogene expression.

Extrachromosomal DNA (ecDNA) is prevalent in human cancers and mediates high expression of oncogenes through gene amplification and altered gene regulation. Gene induction typically involves cis-regulatory elements that contact and activate genes on the same chromosome. Here we show that ecDNA hubs-clusters of around 10-100 ecDNAs within the nucleus-enable intermolecular enhancer-gene interactions to promote oncogene overexpression.

Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions.

Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing of multiregional biopsies in 10 patients with neuroblastoma, a devastating childhood tumour. We observe high spatial and temporal heterogeneity in somatic mutations and somatic copy-number alterations which are reflected on the transcriptomic level.

Transcriptome profiles of the skeletal muscle of mature cows during feed restriction and realimentation.

Objective: Realimentation can compensate for weight loss from poor-quality feedstuffs or drought. Mature cows fluctuate in body weight throughout the year due to nutrient availability. The objective of this study was to determine whether cows that differ in weight gain during realimentation also differ in the abundance of transcripts for enzymes associated with energy utilization in skeletal muscle.

Quantum Mechanical Calculations for Biomass Valorization over Metal-Organic Frameworks (MOFs).

Metal-organic framework (MOF) in biomass valorization is a promising technology developed in recent decades. By tailoring both the metal nodes and organic ligands, MOFs exhibit multiple functionalities, which not only extend their applicability in biomass conversion but also increase the complexity of material designs. To address this issue, quantum mechanical simulations have been used to provide mechanistic insights into the catalysis of biomass-derived molecules, which could potentially facilitate the development of novel MOF-based materials for biomass valorization.

Convergent organization of aberrant MYB complex controls oncogenic gene expression in acute myeloid leukemia.

Dysregulated gene expression contributes to most prevalent features in human cancers. Here, we show that most subtypes of acute myeloid leukemia (AML) depend on the aberrant assembly of MYB transcriptional co-activator complex. By rapid and selective peptidomimetic interference with the binding of CBP/P300 to MYB, but not CREB or MLL1, we find that the leukemic functions of MYB are mediated by CBP/P300 co-activation of a distinct set of transcription factor complexes.

Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig.

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy.

Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma.

MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown.